Variant 11-126293229-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000392678.7(TIRAP):c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 1,232,986 control chromosomes in the GnomAD database, including 377,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 41951 hom., cov: 32)

Exomes 𝑓: 0.79 ( 335770 hom. )

Consequence

TIRAP
ENST00000392678.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42

Variant links:

Genes affected

TIRAP (HGNC:17192): (TIR domain containing adaptor protein) The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

TIRAP links:

ENSG00000254905 (HGNC:):

ENSG00000254905 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-126293229-C-T is Benign according to our data. Variant chr11-126293229-C-T is described in ClinVar as [Benign]. Clinvar id is 2688397.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIRAP	NM_001318777.2 link	c.646+174C>T		intron_variant		ENST00000392679.6	NP_001305706.1	P58753-1A0A024R3M4
TIRAP	NM_001039661.2 link	c.646+174C>T		intron_variant			NP_001034750.1	P58753-1A0A024R3M4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIRAP	ENST00000392679.6 link	c.646+174C>T		intron_variant		2	NM_001318777.2	ENSP00000376446.1		P58753-1

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

111400

AN:

151928

Hom.:

41915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.790

Gnomad AMR

AF:

0.802

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.891

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.776

Gnomad OTH

AF:

0.726

GnomAD4 exome

AF:

0.786

AC:

849810

AN:

1080940

Hom.:

335770

Cov.:

AF XY:

0.790

AC XY:

430528

AN XY:

544930

show subpopulations

Gnomad4 AFR exome

AF:

0.554

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.758

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.881

Gnomad4 FIN exome

AF:

0.779

Gnomad4 NFE exome

AF:

0.775

Gnomad4 OTH exome

AF:

0.779

GnomAD4 genome

AF:

0.733

AC:

111489

AN:

152046

Hom.:

41951

Cov.:

AF XY:

0.743

AC XY:

55227

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.567

Gnomad4 AMR

AF:

0.802

Gnomad4 ASJ

AF:

0.753

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.889

Gnomad4 FIN

AF:

0.800

Gnomad4 NFE

AF:

0.776

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.739

Hom.:

5741

Bravo

AF:

0.723

Asia WGS

AF:

0.926

AC:

3219

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 51. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.28

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over